Polymorph selection by continuous crystallization

This article is motivated by a remarkable observation reported recently by Myerson, Trout, and co‐workers that continuous crystallization is capable of producing metastable polymorphs in stable steady‐state operation. We explain why this phenomenon occurs and give simple design rules for reproducing it in other polymorphic systems. A linear stability analysis gives simple functions of parameters for which one can continuously produce thermodynamically metastable products based only on the relative polymorph dynamics. We demonstrate agreement with two sets of experimental data; L‐glutamic acid grown from aqueous solution and p‐aminobenzoic acid also grown from aqueous solution. For many polymorphic compounds, engineering a process to produce a desired polymorph is as simple as finding a reasonable operating point for the continuous mixed‐suspension mixed‐product removal crystallization process (temperature, residence time, initial supersaturation, etc.) according to the rules reported in this article. © 2016 American Institute of Chemical Engineers AIChE J, 62: 3505–3514, 2016     

Effects of antimicrobial agents on the thermal and mechanical properties of acrylate hydrogel matrices

Polymer materials with antimicrobial activity are prepared by UV polymerization of acrylate and methacrylate mixture at room temperature. The antimicrobials are silver acetate and copper (II) acetate, used without pretreatment. Their chemical stability in the acrylate matrix and their effect on the thermal and mechanical properties of the polymer matrix are investigated as a function of their concentration up to 15 wt %. Physico‐chemical, thermal, rheological, and morphological analyses as well as the surveillance of metal salts release in aqueous medium are conducted. A significant decrease in the thermal stability of the salts introduced into the acrylate matrix is observed after UV treatment. The metal salts also have significant effects on the properties of the matrix. A plasticization and densification of the material associated with an aggregation of salts up to the percolation at the highest concentration are highlighted. At equal concentrations, the effects are more pronounced in the presence of copper salts. The latter was released more slowly than silver salts from acrylate material. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43501.     

Antivirulence Isoquinolone Mannosides: Optimization of the Biaryl Aglycone for FimH Lectin Binding Affinity and Efficacy in the Treatment of Chronic UTI

Uropathogenic E. coli (UPEC) employ the mannose‐binding adhesin FimH to colonize the bladder epithelium during urinary tract infection (UTI). Previously reported FimH antagonists exhibit good potency and efficacy, but low bioavailability and a short half‐life in vivo. In a rational design strategy, we obtained an X‐ray structure of lead mannosides and then designed mannosides with improved drug‐like properties. We show that cyclizing the carboxamide onto the biphenyl B‐ring aglycone of biphenyl mannosides into a fused heterocyclic ring, generates new biaryl mannosides such as isoquinolone 22 (2‐methyl‐4‐(1‐oxo‐1,2‐dihydroisoquinolin‐7‐yl)phenyl α‐d ‐mannopyranoside) with enhanced potency and in vivo efficacy resulting from increased oral bioavailability. N‐Substitution of the isoquinolone aglycone with various functionalities produced a new potent subseries of FimH antagonists. All analogues of the subseries have higher FimH binding affinity than unsubstituted lead 22 , as determined by thermal shift differential scanning fluorimetry assay. Mannosides with pyridyl substitution on the isoquinolone group inhibit bacteria‐mediated hemagglutination and prevent biofilm formation by UPEC with single‐digit nanomolar potency, which is unprecedented for any FimH antagonists or any other antivirulence compounds reported to date.     

A computer simulation approach to evaluating bowl versus inverted bowl assembly line arrangement with variable operation times

A computer simulation model was used to evaluate a bowl versus inverted bowl assembly line arrangement for normal and exponential distributions and variances equal to 1 and 16. The model was developed on the basis of a realistic case problem and applied to a six-station assembly line. The results show that the inverted bowl is superior to the bowl arrangement for a normal distribution in terms of the total elapsed time evaluation criterion; however, with an exponential distribution, the bowl was found better than the inverted bowl for the same criterion. On the basis of the average percentage of working time and the average time in the system evaluation criteria, the bowl was found superior to the inverted bowl for a normal distribution. Similar results were obtained for an exponential distribution with a variance equal to 1, but no definitive inference could be made with a variance equal to 16.     

In situ Diamond Anvil Cell–Raman Spectroscopy and Nanoindentation Study of the Pressure‐Induced Phase Transformation in Pure and Zinc‐Doped β‐Eucryptite

β‐eucryptite (LiAlSiO₄), a member of the family of lithium aluminum silicates, is known to undergo a reversible pressure‐induced phase transformation at ~0.8 GPa to ε‐eucryptite. This study correlates the results between two techniques, in situ diamond anvil cell–Raman spectroscopy and nanoindentation experiments, to explore how doping (substituting Zn for Li) influences this pressure‐induced phase transformation. Diamond anvil cell tests carried up to 3 GPa hydrostatic stress under Raman spectroscopy were compared with nanoindentation results, which provide a more localized, multiaxial stress state. The results indicate that the magnitude of hysteresis observed (difference between the pressures required for the forward and reverse transformation) is lower for Zn‐doped β‐eucryptite; however, the onset of the phase transformation is unchanged by doping with Zn. Furthermore, calculations of activation volume from nanoindentation experiments yield similar values (~0.1 nm³) for pure and Zn‐doped β‐eucryptite, suggesting that the nucleation event that establishes the onset of the phase transformation is the same for both materials.     

Immobilized DNA aptamers as target-specific chiral stationary phases for resolution of nucleoside and amino acid derivative enantiomers

Recently, we described the use of a DNA aptamer as a new target-specific chiral stationary phase (CSP) for the separation of oligopeptide enantiomers (Michaud, M.; Jourdan, E.; Villet, A.; Ravel, A.; Grosset, C.; Peyrin, E. J. Am. Chem. Soc. 2003, 125, 8672). However, from a practical point of view, it was fundamental to extend the applicability of such target-specific aptamer CSP to the resolution of small (bioactive) molecule enantiomers. In this paper, immobilized DNA aptamers specifically selected against D-adenosine and L-tyrosinamide were used to resolve the enantiomers by HPLC, using microbore columns. At 20 degrees C, the adenosine enantioseparation was similar to that classically reported with imprinted CSPs (approximately 3.5) while a very high enantioselectivity was observed for the tyrosinamide enantiomers (the nontarget enantiomer was essentially nonretained on the CSP). The influence of temperature on solute binding and chiral discrimination was analyzed. The binding enthalpic contributions were determined from linear van't Hoff plots. Very large DeltaH values were obtained for the target enantiomers (-71.4 +/- 0.7 kJ/mol for D-adenosine and -139.4 +/- 2.0 kJ/mol for L-tyrosinamide). Such values were consistent with the formation of a tight complex between these analytes and the aptamer CSPs. This work demonstrates that target-specific aptamer CSPs constitute a powerful tool for the resolution of small (bioactive) molecule enantiomers.     

Resilience of super users’ mental models of enterprise-wide systems

Research on information system training has focused primarily on methods, while neglecting the effects of interruption intervals between training and system implementation. This empirical study examines the resilience of accurate mental models of an enterprise-wide system in a large health care facility. Accurate mental models were shown to withstand the passage of time and resulted in superior field performance following a crash conversion. Consistent with prior experimental research, certain types of learners were more likely to acquire these sounder mental models. In large organisations where the simultaneous training of users on a complex system is virtually impossible, scheduling is an important facet of the training paradigm. The main practical implications of this study involve the development of: (1) training programmes emphasising performance on far-transfer tasks, (2) training schedules designed to minimise knowledge erosion, and (3) criteria for selecting highly capable super users.     

Eco-friendly TiO2–AC Photocatalyst for the Selective Photooxidation of 4-Chlorophenol

The influence of surface pH of activated carbon on selectivity of TiO₂ during the photooxidation of 4-chlorophenol on UV-irradiation was studied. Chlorine substitution by p-hydroxylation yielding hydroquinone in equilibrium with benzoquinone and o-hydroxylation to 4-chlorocathecol were detected as the main intermediates in the photooxidation of 4CP. Changes in surface pH of carbons from basic to closely neutral induce a remarkably increase in the production of 4-chlorocatechol by a factor of 22 on TiO₂–AC in comparison of TiO₂ alone. A mechanism of interaction between both solids is proposed to explain changes both in photoactivity and photoselectivity of TiO₂. In conclusion, results showed that TiO₂–AC can be used as an alternative green photocatalyst in organic synthesis.     

Isolation and characterization of inositol sphingophospholipids from Phytophthora parasitica Dastur

Several inositol sphingophospholipids (ISPL) were isolated from mycelia of Phytophthora parasitica Dastur, a phytopathogenic fungus of carnation. The ISPL structures were determined by fast atom bombardment. All ISPL consisted of ceramides linked to inositol phosphate. We investigated the effect of growth conditions on the ISPL produced in four different media that are commonly used for fungal cultures. We showed that P. parasitica Dastur synthesized four major classes of compounds with molecular weights of M_r=751, 807, 835, and 849 containing the 16:1 base and the 16:0 or 20:0 or 22:0 or 22h:1 N-acyl group. The relative abundance of the different ISPL is dependent on growth conditions. This work is dedicated to the memory of Professor G. Michel.